To continue our investigations of the heterogeneous mechanisms by which human monocytes regulate the function of the effector cells in the immune response, we measured enzymatic changes associated with cell membrane activation that precede as well as follow DNA synthesis as measured by 3H-thymidine incorporation. Our hypothesis was that both stimulatory and suppressive signals provided by cells of the monocyte-macrophage lineage cause cell membrane perturbations that result in measurable changes in the activities of ornithine decarboxylase (ODC), cAMP-dependent protein kinase, and calcium phospholipid protein kinase. We found that phytohemagglutinin has little effect on the ODC activity in T lymphocytes or monocytes. T-lymphocyte activation as measured by ODC induction required two signals: the first being mitogen or antigen and the second provided by macrophages or their products, specifically interleukin 1. Further studies showed that Cyclosporin A inhibited both mitogen-\and alloantigen-stimulated induction of ODC. In contrast, Cyclosporin A did not inhibit the induction of ODC, cAMP-dependent protein kinase, or calcium phospholipid protein kinase in murine T-cell tumor lines. (CS)